Chlamydial infections of the urogenital tract constitute the most common cause of bacterial sexually transmitted diseases (STDs) of humans. Moreover, chlamydial STDs are an important co-factor in the transmission of HIV. Effective control of chlamydial STDs will only likely be achieved through the development of an efficacious vaccine. Despite considerable effort there has been little progress towards the development of a chlamydial vaccine. This lack of progress is largely due to an inadequate understanding of host immunity to chlamydial infection; particularly those aspects of the immune response that confer adaptive protective immunity following infection. The goal of this project is to study the cellular and molecular basis of protective immunity against chlamydial infections of the urogenital tract and to utilize this information to design efficacious vaccines for the prevention of chlamydial caused STDs of humans. We have used a mouse model of chlamydial infection of the female urogenital tract that closely mimics human chlamydial infections to better define immune mechanisms that function in adaptive protective immunity to infection. By utilizing targeted gene knock out (KO) mice deficient in specific T and B cell functions and T cell secreted effector cytokines we have demonstrated that CD4+ T cells are the key T cell phenotype that confers protective immunity against chlamydial urogenital tract infection. Resolution of both primary and secondary chlamydial urogenital tract infections was shown to be mediated by CD4+ Th1 cells, whereas resistance to re-infection was mediated by local chlamydial specific sIgA (CD4+ Th2 dependent immunity). These findings indicate that an efficacious chlamydial vaccine for use in humans will require immunization capable of inducing both chlamydial specific CD4+ Th1 cell mediated immunity as well as local sIgA antibody. Future plans will focus on defining the effector mechanism(s) by which CD4+ Th1 resolve chlamydial infection and identification of chlamydial antigens recognized by protective Th1 cells. Protective antigens will then be tested as experimental vaccines in the mouse model with particular emphasis on the targeted delivery of antigens capable of generating chlamydial specific CD4+ T cell immunity at the urogenital tract mucosa.